The overall aim of Project 3 is to test hypotheses about mechanisms through which perceived stress and mood alter HIV-related immune function during early HIV infection. Stress and depressed mood are associated with more rapid declines in CD4 cell counts, the key immunologic endpoint through which disease progress occurs in HIV. Recent evidence suggests several plausible biological mechanisms that are influenced by the neuroendocrine system and are potentially important factors in HIV disease progression: (1) Increased CCR5 and CXCR4 receptor expression. These co-receptors for HIV cell entry are regulated in part by the autonomic nervous system and increased expression of these co-receptors may facilitate HIV cell entry and replication. (2) Increased CD8 T cell activation, which is strongly linked to more rapid loss of CD4 T cells. (3) Changes in cytokine expression and decreased NK cell function and plasmacytoid dendritic cells (PDC) that impair immune responses to HIV. For this project we will study in detail immune function and phenotype in a subset of 120 participants from the randomized, controlled trial of Mindfulness Based Stress Reduction (MBSR) in early HIV infection (Project 1 of this application). Data from neuroendocrine and autonomic nervous system (ANS) studies (Project 2) will be linked to data from the immune assays performed in this study (Project 3) to define further the pathways through which perceived stress and mood influence the immune system in early HIV via the neuroendocrine system. Studying these pathways will advance our understanding of mind-body interactions in HIV and the mechanisms through which interventions such as MBSR may affect immune function in general and HIV disease progression in particular. We will test hypotheses that higher perceived stress and depressed mood at baseline are associated with higher CCR5 and CXCR4 receptor expression on CD4+ T cells (co-receptors for HIV entry), higher CD8 T cell activation, less advantageous cytokine levels, and lower levels of NK and PDC cells, and that decreases in stress and depression will predict improvement in each of these parameters. We will also test whether MBSR improves each of these immune parameters, and whether changes are linked with hypothesized neuroendocrine influences.